title: Methyl 5-chloro-4,5-didehydrojasmonate (J7) inhibits macrophage-derived chemokine production via down-regulation of the signal transducers and activators of transcription 1 pathway in HaCaT human keratinocytes.
abstract: Jasmonates are lipid-based stress hormones that are critical for the defense of plants against insects. Two naturally occurring jasmonates, jasmonic acid and methyl jasmonate, have recently been explored for their efficacy as anti-cancer agents. Furthermore, certain synthetic jasmonates (e.g., the cyclopentenone isoprostane J2) exert anti-inflammatory actions in lipopolysaccharide (LPS)-challenged murine macrophages via down-regulation of chemokines and other inflammatory mediators. Chemokines participate in the development and progression of many inflammatory disorders, such as atopic dermatitis (AD) and Crohn's disease, as exemplified by the role of macrophage-derived chemokine (MDC/CCL22) in the pathology of AD. The current study therefore investigated the impact of jasmonate derivatives (jasmonic acid and methyl jasmonate) and their synthetic analogues (J2 and J7) on the expression of MDC in interferon (IFN)-γ- and tumor necrosis factor (TNF)-α-stimulated HaCaT human keratinocytes, as well as the attendant mechanism of action. Jasmonic acid, methyl jasmonate, and J2 failed to inhibit the cytokine-stimulated production of MDC. By contrast, J7 suppressed the mRNA and protein expression levels of MDC in a dose-dependent manner. Moreover, J7 diminished the activation of signal transducers and activators of transcription 1 (STAT1), but had no inhibitory effect on the nuclear factor kappa B (NF-κB) or mitogen-activated protein kinase (MAPK) pathways. These results demonstrate that J7 impairs IFN-γ- and TNF-α-induced inflammatory chemokine production by targeting the STAT1 pathway.
authors.affiliation: Department of Medicine, Jeju National University School of Medicine.
authors.forename: Gyeoung-Jin
authors.initials: GJ
authors.lastname: Kang
authors.forename: Hung-The
authors.initials: HT
authors.lastname: Dang
authors.forename: Sang-Chul
authors.initials: SC
authors.lastname: Han
authors.forename: Na-Jin
authors.initials: NJ
authors.lastname: Kang
authors.forename: Dong-Hwan
authors.initials: DH
authors.lastname: Koo
authors.forename: Young Sang
authors.initials: YS
authors.lastname: Koh
authors.forename: Jin Won
authors.initials: JW
authors.lastname: Hyun
authors.forename: Hee-Kyoung
authors.initials: HK
authors.lastname: Kang
authors.forename: Jee H
authors.initials: JH
authors.lastname: Jung
authors.forename: Eun-Sook
authors.initials: ES
authors.lastname: Yoo
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000633:toxicity*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D003517:Cyclopentanes / Q000737:chemistry* / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects*; D005231:Fatty Acids, Unsaturated / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D054883:Oxylipins / Q000737:chemistry / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000819:agonists / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D018925:Chemokines; D003517:Cyclopentanes; D005231:Fatty Acids, Unsaturated; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D016328:NF-kappa B; D054883:Oxylipins; D012333:RNA, Messenger; D050794:STAT1 Transcription Factor; D014409:Tumor Necrosis Factor-alpha; C555027:methyl 5-chloro-4,5-didehydrojasmonate; C011006:jasmonic acid; D007371:Interferon-gamma; D020928:Mitogen-Activated Protein Kinases